Experimental and theoretical evaluation of nanodiamonds as pH triggered drug carriers

Nanodiamond (ND) and its derivatives have been widely used for drug, protein and gene delivery. Herein, experimental and theoretical methods have been combined to investigate the effect of pH on the delivery of doxorubicin (DOX) from fluorescein labeled NDs (Fc-NDs). In the endosomal recycling process, the nanoparticle will pass from mildly acidic vesicle to pH ≈ 4.8; thus, it is important to investigate DOX release from NDs at different pH values. Fc-NDs released DOX dramatically under acidic conditions, while an increase in the DOX loading efficiency (up to 6.4 wt%) was observed under basic conditions. Further theoretical calculations suggest that H+ weakens the electrostatistic interaction between ND surface carboxyl groups and DOX amino groups, and the interaction energies at pH 7 are 10.4 kcal mol−1, 25.0 kcal mol−1 and 27.0 kcal mol−1 respectively. Cellular imaging experiments show that Fc-NDs are readily ingested by breast adenocarcinoma (BA) cells and cell viability tests prove that they can be utilized as a safe drug delivery vehicle. Furthermore, pH triggered DOX release has been tested in vitro (pH 7.4 and pH 4.83) in breast adenocarcinoma (BA) cells.

[1]  Theresa M Reineke,et al.  Theranostics: combining imaging and therapy. , 2011, Bioconjugate chemistry.

[2]  Thierry Gacoin,et al.  Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells. , 2011, Small.

[3]  R. Boukherroub,et al.  Preparation and characterization of Zonyl-coated nanodiamonds with antifouling properties. , 2011, Chemical communications.

[4]  A. Goga,et al.  Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment , 2011, Science Translational Medicine.

[5]  A. Schrand,et al.  Temporal and mechanistic tracking of cellular uptake dynamics with novel surface fluorophore-bound nanodiamonds. , 2011, Nanoscale.

[6]  Thomas Meinhardt,et al.  Pushing the Functionality of Diamond Nanoparticles to New Horizons: Orthogonally Functionalized Nanodiamond Using Click Chemistry , 2011 .

[7]  George C Schatz,et al.  Atomistic simulation and measurement of pH dependent cancer therapeutic interactions with nanodiamond carrier. , 2011, Molecular pharmaceutics.

[8]  Jui‐I Chao,et al.  Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy , 2010, Nanotechnology.

[9]  R. Boukherroub,et al.  Functionalization of diamond nanoparticles using "click" chemistry. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[10]  Jinfang Zhi,et al.  Nanodiamond as the pH-responsive vehicle for an anticancer drug. , 2010, Small.

[11]  Giovanni Scalmani,et al.  Continuous surface charge polarizable continuum models of solvation. I. General formalism. , 2010, The Journal of chemical physics.

[12]  H. García,et al.  Fenton-treated functionalized diamond nanoparticles as gene delivery system. , 2010, ACS nano.

[13]  D. Ho Beyond the sparkle: the impact of nanodiamonds as biolabeling and therapeutic agents. , 2009, ACS nano.

[14]  Kuang-Kai Liu,et al.  Endocytic carboxylated nanodiamond for the labeling and tracking of cell division and differentiation in cancer and stem cells. , 2009, Biomaterials.

[15]  Dean Ho,et al.  Polymer-functionalized Nanodiamond Platforms as Vehicles for Gene Delivery Keywords: Nanodiamonds · Gene Delivery · Nanocarrier · Transfection · Low Molecular Weight Polyethyleneimine (lmw Pei) , 2022 .

[16]  D. Ho,et al.  Nanodiamonds as vehicles for systemic and localized drug delivery , 2009, Expert opinion on drug delivery.

[17]  N. Rozhkova,et al.  Consequences of strong and diverse electrostatic potential fields on the surface of detonation nanodiamond particles , 2009 .

[18]  Y. Gogotsi,et al.  Wet chemistry route to hydrophobic blue fluorescent nanodiamond. , 2009, Journal of the American Chemical Society.

[19]  Yury Gogotsi,et al.  Nanodiamond-polymer composite fibers and coatings. , 2009, ACS nano.

[20]  Patrick Georges,et al.  Detection of single photoluminescent diamond nanoparticles in cells and study of the internalization pathway. , 2008, Small.

[21]  J. Boudou,et al.  Peptide‐Grafted Nanodiamonds: Preparation, Cytotoxicity and Uptake in Cells , 2008, Chembiochem : a European journal of chemical biology.

[22]  A. Krueger,et al.  New carbon materials: biological applications of functionalized nanodiamond materials. , 2008, Chemistry.

[23]  Eiji Ōsawa,et al.  Recent progress and perspectives in single-digit nanodiamond , 2007 .

[24]  Michael Sternberg,et al.  Crystallinity and surface electrostatics of diamond nanocrystals , 2007 .

[25]  Erik Pierstorff,et al.  Active nanodiamond hydrogels for chemotherapeutic delivery. , 2007, Nano letters.

[26]  Hua Ai,et al.  Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. , 2006, Nano letters.

[27]  Francis C Szoka,et al.  Designing dendrimers for biological applications , 2005, Nature Biotechnology.

[28]  Huan-Cheng Chang,et al.  Bright fluorescent nanodiamonds: no photobleaching and low cytotoxicity. , 2005, Journal of the American Chemical Society.

[29]  Victor S-Y Lin,et al.  Stimuli-responsive controlled-release delivery system based on mesoporous silica nanorods capped with magnetic nanoparticles. , 2005, Angewandte Chemie.

[30]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[31]  You Han Bae,et al.  Super pH-sensitive multifunctional polymeric micelle. , 2005, Nano letters.

[32]  W. Steglich,et al.  Simple Method for the Esterification of Carboxylic Acids , 1978 .

[33]  Yury Gogotsi,et al.  The properties and applications of nanodiamonds. , 2011, Nature nanotechnology.